Today, state-of-the-art radiotherapy provides excellent benefits for patients with early stage and radiosensitive cancers. However, these benefits diminish for patients with radioresistant tumors, such as brain or pancreas cancers, and patients with late stage tumor. For these patients radiation needed to eradicate radioresistant tumor can cause intolerable or fatal radiation damage to normal tissue. This is especially the case for pediatric patients, whose rapidly developing normal tissues are often more radiosensitive than their tumors, and who therefore cannot tolerate radiotherapy that would be curative for adults with the same disease. An ideal radiotherapy treatment is one with sharp tissue type selectivity - it intrinsically kills tumor tissue and leave normal tissue including central nerve system tissue undamaged. Microbeam radiation therapy (MRT) may be just such a perfect radiotherapy. Convincing animal studies have shown that a single MRT treatment of ultrahigh dose (100s Gy) effectively eradicated tumor but the same radiation caused no harm to normal tissue including developing central nerve system. Despite of its enormous clinical impact MRT has not been used on human. There are two major bottlenecks in translating MRT from bench-side to bedside: 1) the lack of understanding of the underlying mechanism and 2) the lack of MRT irradiation devices. There are only two animal research MRT facilities in the world and no human MRT system exists today. Most cancer researchers today have no access to MRT radiation and thus cannot carry out MRT mechanistic studies that are needed to the translation to clinical application. We propose to develop the world first desktop image-guided MRT system for cancer research now and potential clinical treatment in the future. The device is based on the carbon nanotube (CNT) field emission technology pioneered by our team at UNC. The key challenge for a desktop MRT system is dose rate and the enabling technology is CNT-based spatially distributed x-ray source array. To carry out the proposed research we assembled a highly multidisciplinary and well-integrated research team including nano-material scientists, engineers, medical physicists, and cancer biologists at UNC and a local startup company, XinRay Systems. We have already carried out initial feasibility studies and they indicate that the novel desktop system is capable of producing characteristic MRT radiation comparable to the MRT radiation produced by the synchrotron facilities. The potential impact of the proposed work to cancer patients and health care system is inconceivably high. If human patients response to MRT in similar ways as reported in numerous MRT animal studies, MRT will literally revolutionize cancer treatment. Cancer patients including pediatric patients and those with radioresistant tumors, to whom conventional radiotherapy has not be effective, will have a much improved treatment response, which leads to a better survival and quality of life. Instead of 20-40 daily treatments in conventional radiotherapy patients will receive a single MRT treatment, which itself can be a tremendous practical benefit to patients living with cancer and their families. There will be a drastic decrease in radiotherapy cost, currently a burden to our increasingly expensive health care system. Because of the relative low cost and compactness of the proposed MRT system, once developed, the MRT treatment technology can be made readily available and affordable for widespread research and clinical application in US and beyond to benefit all cancer patients. Once the proposed technology is successfully developed and its feasibility demonstrated, we plan to commercialize this technology and make it available for the broad radiation oncology community. Our team has a demonstrated track record of conducting successful translational biomedical research, and moving new technologies from academic labs to the market place. A recent success is an innovative high speed tomosynthesis image guided radiation therapy system developed jointly with Siemens Oncology using the same enabling nanotechnology. The image guidance system is capable of 3D imaging in real time and during radiation delivery, a highly desirable function that does not exist in all current imaging systems. The combination of UNC's academic multidisciplinary research expertise and innovation with industrial know-how in device fabrication from XinRay and its parent companies makes our team perfectly suited to carry out the proposed novel MRT technology development and its future development for clinical application. Public Health Relevance: The fundamental challenge of radiotherapy is to treat cancer patient effectively and safely. Today, state-of-the-art radiotherapy provides excellent benefits for patients with early stage and radiosensitive cancers. These benefits diminish for patients with radioresistant tumors, such as brain or pancreas cancers, and patients with late stage tumors. For these patients radiation needed to eradicate radioresistant tumor can cause intolerable or fatal radiation damage to normal tissue. This is especially the case for pediatric patients, whose rapidly developing normal tissues are often more radiosensitive than their tumors, and who therefore cannot tolerate radiotherapy that would be curative for adults with the same disease. Microbeam Radiotherapy (MRT) is a unique form of radiation that has shown an extraordinary ability to eradicate tumor and spare normal tissue in numerous animal studies. Despite of its enormous clinical impact MRT has not been used on human, partially due to the lack of understanding of the underlying mechanism, which in turn is hindered by the lack of MRT devices. MRT radiation is technically extreme difficult to produce and it is performed in only two institutions in the world with synchrotron facilities. We propose to develop the world first desktop image-guided MRT system for cancer research and treatment. The device is based on the carbon nanotube (CNT) field emission technology pioneered by our team at UNC. To carry out the proposed research we assembled a highly multidisciplinary and well-integrated research team including physicists, engineers, medical physicists, and cancer biologists at UNC and a local startup company, XinRay Systems. We have already carried out initial feasibility studies and they indicate that the novel desktop system is capable of producing characteristic MRT radiation comparable to the MRT radiation produced by the synchrotron facilities. The potential impact of the proposed work to cancer patients and health care system is inconceivably high. If human patients response to MRT in similar ways as reported in numerous MRT animal studies, MRT will literally revolutionize cancer treatment.